Hereditary Breast & Ovarian Cancer Syndrome

Mutations in the BRCA1 gene are associated with an increased risk of breast cancer in both men and women, as well as several other types of cancer. These mutations are present in every cell in the body and can be passed from one generation to the next. As a result, they are associated with cancers that cluster in families. However, not everyone who inherits a mutation in the BRCA1 gene will develop cancer. Other genetic, environmental, and lifestyle factors also contribute to a person's cancer risk.

Most BRCA1 gene mutations lead to the production of an abnormally short version of the BRCA1 protein or prevent any protein from being made from one copy of the gene. As a result, less of this protein is available to help repair damaged DNA or fix mutations that occur in other genes. As these defects accumulate, they can trigger cells to grow and divide uncontrollably to form a tumor.

Many of the same BRCA1 gene mutations that increase the risk of breast cancer (described above) also increase the risk of ovarian cancer. Families with these mutations are often said to be affected by hereditary breast and ovarian cancer syndrome. Women with BRCA1 gene mutations have a 35 to 60 percent chance of developing ovarian cancer in their lifetimes, as compared with 1.6 percent in the general population.

BRCA is short for "breast cancer gene." A BRCA genetic test uses a sample of your blood, saliva (spit), or cells from inside of your cheek to look for changes in your BRCA1 and BRCA2 genes. Genes are parts of DNA in your cells that you inherit from your parents. You inherit two copies of each gene, one from each parent. Genes carry information that controls what you look like and how your body works.

BRCA is a type of gene called a "tumor suppressor." Tumor suppressor genes provide instructions for making proteins that help prevent or slow the growth of cells that may become tumors. The proteins work by:

• Preventing cells from dividing too quickly to make new cells.
• Repairing damaged DNA in cells.
• Starting the normal process of cell death in cells that can't be repaired.

If you have certain changes (or variations) in a BRCA gene, the gene or the protein it makes may not work well or may stop working completely. As a result, your cells may grow and divide out of control, which can lead to tumors and cancer.

Other names: BRCA gene test, BRCA gene 1, BRCA gene 2, breast cancer susceptibility gene1, breast cancer susceptibility gene 2

This test is used to find out if you have harmful changes in your BRCA1 or BRCA2 genes that increase your risk of getting:

• Breast cancer. This is cancer of the breast tissue. It mostly affects females, but harmful BRCA variations can also increase the breast cancer risk for males.
• Ovarian cancer. This is cancer of the female reproductive glands where eggs form.
• Prostate cancer. This is cancer of the male reproductive gland that makes fluid for semen.
• Pancreatic cancer. This is cancer of the pancreas, an organ that helps you digest food and makes important hormones.

Harmful variations in the BRCA gene are rare. They affect only about 0.2% of the U.S. population. So, BRCA testing is not recommended for most people.

You and your family members are more likely to have a BRCA1 or BRCA2 variation if either side of your family has a strong history of:

• Female breast cancer diagnosed under the age of 50.
• Triple negative breast cancer (an especially aggressive form less likely to respond to treatment) diagnosed under the age of 60.
• Male breast cancer.
• Cancer of the ovaries, fallopian tubes (tubes connecting the ovaries to the uterus), or peritoneum (tissue that covers your belly organs).
• Prostate cancer that spreads to other parts of the body (metastatic cancer).
• Pancreatic cancer.

If you're concerned that you may have a harmful variant in the BRCA1 or BRCA2 gene, your health care provider or a genetic counselor can review your personal and family health history. to see if you need this test.

You should also talk to your provider about testing if you've had any of these cancers and/or are of Ashkenazi (Eastern European) Jewish descent. BRCA variations are much more common in those with Ashkenazi Jewish ancestry compared with the general population.

A BRCA test can use either a sample of your blood, saliva, or a cheek swab.

• For a blood test: A health care professional will take a blood sample from a vein in your arm, using a small needle. After the needle is inserted, a small amount of blood will be collected into a test tube or vial. You may feel a little sting when the needle goes in or out. This usually takes less than five minutes.
• For a saliva test: You'll spit into a container or use a cotton pad to soak up some saliva.
• For a cheek swab: A health care professional will use a special swab or brush to take a sample from your cheek. You may have the option of doing it yourself.

You may be able to use an at-home saliva test kit to check for the three most common harmful variations in BRCA genes. But there are more than 1000 known variations. A home test can't rule out all of them. If you decide to use an at-home test kit, be sure to follow all your provider's or the kit's instructions for collecting a sample and getting that sample to a lab.

• For a blood test: You don't need any special preparations.
• For a saliva test: A half hour before the test, you may need to stop eating, drinking, or smoking. Follow all the instructions your provider gives you or the instructions in an at-home kit.
• For a cheek swab: You may be asked to rinse your mouth before the test.

With any type of genetic test, you may want to meet with a genetic counselor first to see if testing is right for you. Your counselor can explain the pros and cons of learning more about your cancer risk. After your test, a counselor can help with the medical and emotional impact that your results may have on you and your family.

• There is very little risk to having a blood test. You may have slight pain or bruising at the spot where the needle was put in, but most symptoms go away quickly.
• There are no risks linked to providing a saliva sample or having a cheek swab.

Your provider or genetic counselor will need to explain how your results affect your risk for certain cancers. That's because the meaning of your test results depends on the exact type of BRCA variant you have and your personal and family health history.

In general, your results may be reported using these terms:

• A negative (normal) result means that the test didn't find any harmful changes in your BRCA genes. How this affects your cancer risk depends on whether you've already had cancer and whether a member of your family has a harmful BRCA variant.
• An uncertain result may also be called a "variant of uncertain significance (VUS)". It means that a variant in your BRCA genes was found, but researchers don't know whether that variant causes cancer.
• A positive result may also be called a "likely pathogenic variant." It means that you have a harmful gene variant that is known to increase the risk of certain cancers. But the test cannot tell whether you will develop cancer.

Learn more about laboratory tests, reference ranges, and understanding results.

Not everyone who has a harmful variant in BRCA1 or BRCA2 will get cancer. If your results show that you have a harmful variant in your BRCA genes, talk with your provider about ways to lower your cancer risk. You may discuss:

• Your schedule for cancer screening tests. Your provider may recommend that you get tested sooner and more often than usual.
• Taking certain medicines and/or having surgery to reduce the risk of cancer. Surgery may include removing both breasts and/or the ovaries and fallopian tubes. Medicines such as tamoxifen and raloxifene can also reduce your cancer risk by controlling the levels of estrogen (a hormone that plays a key role in female reproductive health) in your body.